Autoimmune Diseases

FAQ

A. Questions about RA

1. What is RA?

Rheumatoid is a progressive disease that involves pain and swelling of the joints.

2. What causes RA?

The specific causes of RA are unknown, but it is a systemic autoimmune disease, that is, a person's immune system inappropriately attacks his/her own tissue.

3. How many people have RA?

More than 1.5 million U.S. adults have RA, and women are three-times more likely to be afflicted than men.

4. What are the treatments for RA?

There are three broad categories of drugs for RA treatment, including: 1) Disease modifying anti-rheumatic drugs (DMARDs) that reduce the rate of damage to joints, and include methotrexate, leflonamide, and sulfasalazine; 2) anti-inflammatory drugs, including glucocorticoids such as prednisone and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, and diclofenac; and 3) biologics such as Embrel and Remicade that block proteins that mediate or modulate inflammatory processes.

5. What are the side effects of the RA treatments?

Each major drug for RA has several significant side effects. For example, NSAIDs can cause gastric bleeding and other cardiovascular effects, and many of the biologics are immunosuppressive and thus increase the risk of bacterial or viral infection.

6. How effective are the RA current drugs?

Most current drugs offer significant improvement in RA symptoms in some patients, and clinical remission is possible. RA drugs are often used in combination, and finding the most effective combination for a particular patient often involves a physician to change drugs over time.

7. How long do you have to take the current RA drugs?

The goal of drug treatment is clinical remission, and with appropriate therapy many patients can achieve remission. However, RA symptoms can flare, so drugs are used to maintain remission. Thus, in most cases, patients diagnosed with RA will be in treatment for the rest of their lives.

8. What is the annual patient cost for treatment?

The cost to the patient will depend upon insurance and other benefits, but retail prices for RA drugs range from dollars per month for older, generic DMARDs and NSAIDs to $1000-$3000 per month for newer biologics.

9. What is the total market for RA drugs?

In 2013 the leading biologics approved for RA generated more than $18 billion in sales world wide.

10. What are the major drugs for the treatment of RA?

The most commonly prescribed treatment for RA is methotrexate.Enbrel is the biggest drug with 2013 worldwide sales exceeding $8 billion.

B. Questions about PRTX-100

1. What is PRTX-100?

2. How is PRTX-100 made?

Staph A is grown by fermentation in an FDA certified production facility, the bacteria are disrupted and through a number of purification steps PRTX-100 is isolated.

3. How does PRTX-100 work?

While the precise mechanism of action remains unknown, PRTX-100 binds selectively to B-cells via surface immunoglobulin and in mouse studies results in depletion of B-cells of the VH3 lineage.

4. What are the side effects of PRTX-100?

At the current stage of human clinical testing, no serious treatment-related adverse effects have been identified aside from symptoms associated with intravenous administration of the drug.

5. What is the efficacy of PRTX-100?

The efficacy of PRTX-100 has not been conclusively established but pre-clinical and clinical data strongly indicates it will have an efficacy profile equal to the leading biologics.

6. How long do you have to take PRTX-100?

Unknown at this time.

7. What will be the annual patient cost for PRTX-100 treatment?

Unknown at this time but will much cheaper than current treatments.

C. Questions about the South African Trial (103 Trial)

1. What type of trial was it?

The 103 Trial was an escalating dose cohort phase 1b trial in which patients with active RA despite being on methotrexate therapy received multiple doses of PRTX-100.

2. Why did you do the trial in SA?

The trial was run in South Africa for a variety of reasons, including the ability to recruit eligible patients and the quality of the clinical investigators.

3. How many sites participated in the trial?

Three sites participated

4. What were the major inclusion criteria?

We enrolled adult patients that had been on a stable dose of methotrexate and had active RA as defined by swollen and tender joints and high titers of C-reactive protein.

5. What were the major exclusion criteria?

We excluded patients with autoimmune diseases other than RA, patients with history of malignancy, HIV, diabetes, heart disease, severe infection, or respiratory disease.

6. What was the ratio of active to placebo patients?

29 patients received PRTX-100, and 8 patients receive a placebo.

7. Did you have a Safety Monitoring Committee?

Yes

8. How would you describe any drug related Serious Adverse Events?

There were no Serious Adverse Events (SAEs) related to the drug. Five SAEs occurred in four patients: three in the PRTX-100 group and two in the placebo group. SAEs included colitis, a broken arm, and worsening of RA.

9. How would you describe any drug related Adverse Events?

Adverse Events were related to intravenous injection of PRTX-100, and included mild nausea and dizziness. In all cases the reaction resolved shortly after the injection.

10. Was a maximum tolerated dose reached?

No

11. How many patients were there in the trial?

37

12. How many patients were there per cohort?

Up to 10 patients per cohort, with up to 8 receiving PRTX-100 and up to 2 receiving placebo

13. How many cohorts were there?

There were four dose escalating cohorts

14. What was the dose per cohort?

Cohorts were dosed with 0.15, 0.45, 0.90, and 1.50 μg/kg body weight. Each dosing cohort included up to 2 patients receiving placebo.

15. Don't you mean milligrams instead of micrograms?

No

16. What was the duration of the treatment?

Subjects received four doses on days 0, 7, 14, and 21.

17. How would you characterize the safety of the drug?

We concluded that PRTX-100 is generally safe and well tolerated at the doses employed in this study.

18. How did you measure efficacy?

We used a well-validated scoring metrics for RA, the DAS-CRP and the CDAI, measured at various times during the study. The measurements included a count of swollen and painful joints, the patient's subjective global health assessment, and in the case of DAS-CRP, a blood-based measurement of inflammation.

19. How would you characterize the efficacy of the drug?

The 103 Trial suggested that some patients responded well with PRTX-100 at the highest (1.50 μg/kg) dose level.

3. What were the differences compared to the SA 103 Trial?

The 104 Trial was 5 cohorts, with the first cohort (Cohort 1) starting at the highest dose level from the 103 Trial (1.5 micrograms/kg) and then each cohort thereafter escalating to higher doses than the 103 Trial. The last cohort (Cohort 5) in addition to the five weekly doses also included fixed weight doses and up to 4 additional monthly maintenance doses.

4. What were the major inclusion criteria?

To be included, patients had to have active rheumatoid arthritis despite receiving DMARD therapy (methotrexate or leflunomide) for at least 12 weeks, 8 weeks on a stable dose. Patients must also be at least 18 years old and willing and able to give written informed consent for participation.

5. What were the major exclusion criteria?

Patients were excluded in if they had a diagnosis for any other inflammatory arthritis (psoriatic arthritis, spondloarthropathy, gout) or other prior or current medical conditions.

6. What was the ratio of active to placebo patients?

In an initial dose-escalation phase, patients were randomized 3:1 to active:placebo groups.

7. Was there a Safety Monitoring Committee?

Yes

8. How many patients were enrolled in the trial?

A total of 61 patients were enrolled in 5 cohorts.

9. How many patients will there be per cohort?

Six patients received active treatment in each dose group.

10. What was the duration of the treatment?

Five weeks of treatment.in Cohorts 1-5. In Cohort 5, there were up to four additional monthly maintenance doses for many of the patients.

11. How long will you follow the patient after the end of treatment?

Up to one year of post-treatment follow up.

12. When did the trial end?

The 104 Trial concluded in August 2014, approximately 20 months after initiation.